The use of bacterial cells to produce protein-based therapeutics is increasing in commercial importance. One of the goals in developing a bacterial expression system is the production of high quality target polypeptides quickly, efficiently, and abundantly. An ideal host cell for such an expression system would be able to efficiently utilize a carbon source for the production of a target polypeptide, quickly grow to high cell densities in a fermentation reaction, express the target polypeptide only when induced, and grow on a medium that is devoid of regulatory and environmental concerns. There are many hurdles to the creation of a superior host cell. First, in order to produce a recombinant polypeptide, an expression vector encoding the target protein should be inserted into the host cell. Many bacteria are capable of reverting back into an untransformed state, wherein the expression vector is eliminated from the host. Such revertants can decrease the fermentation efficiency of the production of the desired recombinant polypeptide.
Fiber-optic probes can be used to determine cell concentration measurements in the fermentation process. These determinations are often performed off-line via an optical density analyzer, for example, a visible light spectrophotometer. On-line and in situ probes are available but they frequently require calibration processes specific for each fermentation process. One probe that can be used in this manner is the fiber-optic probe of U.S. Pat. No. 4,707,134 (the MiniView suspended solids gauge from Guided Wave, Inc., Rancho Cordova, Calif. (formerly Optical Solution Inc.)). This probe can be used for in situ detection and measurement of the intensity of light scattered by particles suspended in a transparent or translucent fluid medium. However, when the effective optical density of the medium exceeds about 50, the response can flatten out. Some mediums in need of analysis, such as biological growth media containing bacteria, can have a turbidity expressed in terms of optical density in the range of from about 50 to even as high as 200. Thus, it could be advantageous if a fiber-optic probe system were discovered that produced a more linear response in the optical density range of from about 50 to about 200.